The effects of phentolamine on calcium and phosphate metabolism were studied in young female rats. The i.p. administration of phentolamine (1.3 to 35.1 mg/kg) produces hypocalcemic and hypophosphatemic responses that resemble those produced by the hormone calcitonin. The hypocalcemic response to phentolamine reaches a maximum one hour post injection and blood calcium concentrations return to normal three hours following drug administration. Bilateral nephrectomy does not negate the hypocalcemic effect of phentolamine indicating that the drug effect is not mediated by increased renal excretion of calcium. Thyroparathyroidectomy inhibits the hypocalcemic activity of phentolamine. The mechanism of action of phentolamine with respect to changes in circulating calcium does not involve alpha adrenergic receptor blockage since large doses of tolazoline do not result in alterations in the plasma concentration of calcium. Labeling experiments with 45Ca indicate that the administration of phentolamine results in an inhibition of bone resorption.